Medical testing has long been a staple in healthcare, and often serves as the starting point for providing diagnostic and (if necessary) ameliorative or palliative care. For certain conditions, testing using fluid samples collected from a patient have become the preferred method for analysis. Rapid diagnostic tests (RDTs) at point-of-care (POC) are one type of medical testing. Though convenient, the usage of RDTs has several main critiques that prevent such applications from being more widely adopted relative to centralized laboratory testing. These critiques range from a perceived higher cost and lower accuracy and precision of RDTs relative to central laboratory tests; issues with data traceability due to lack of device connectivity; and a potentially higher incidence rate of operator error. While recent POC devices have attempted to address some of these issues with lower material costs, data transmission capabilities, and improved standards and qualifications, concerns regarding performance and reliability still persist.
The POC market is comprised of many lateral flow or passive flow-through devices. These are technologies that use capillary-driven flow to perform assays on fluid samples. Passive flow generally limits these devices from yielding precise, quantitative results. Likewise, lateral flow devices provide only qualitative or semi-quantitative results due to a limited control of reagent and sample handling that could otherwise be used to optimize assay conditions. The use of additional components such as external pumps to accomplish active flow control capabilities or new biosensors to increase sensitivity can be used to mitigate these disadvantages, but would also add complexity into the manufacturing process that may be undesirable.
The ability to perform sample preparation on fluids such as separating and/or extracting particles and cells based on size is highly desirable for a rapid diagnostic. Separation processes for diagnostics may include centrifugation, filtration, precipitation, adsorption, chromatography, and extraction for separating by particles by size, density, shape, viscosity, and other physical and chemical properties. Centrifugation has long been the standard lab technique for separating particles. However, centrifugation equipment is not suitable for POC applications. Moreover, operators can often encounter difficulties when centrifuging small sample volumes because samples are easily lost during pipetting and decanting steps. Automated robotic sampling can address the issues with handling small sample volumes however; these machines are costly and can be inefficient or even prohibitive for many healthcare providers. The other methods of separation require special chemistries and handling which would introduce operator errors and quantitative inaccuracies and imprecision in the results of the diagnostic device.
Blood sample preparation is another important step when developing a point-of-care diagnostic device. Rapid plasma extraction from whole blood is required to prevent cellular components from interfering with the detection analysis which is often performed optically in a POC device. In rapid diagnostic devices, commercially available filters are integrated into the device to extract plasma. However, manufacturing these filters requires complex and costly processing with multiple reagents. Other microfluidic strategies to extract plasma include the bifurcation law, hydrodynamics, filtration, and magnetophoresis. Unfortunately, many of these strategies have practical limitations in cost, time, scale-up, and plasma yield that make them less than ideal.